1.0 OBJECTIVE:
1-1 To lay down a procedure for Qualification
and Re-qualification of steam sterilizers / Autoclaves.
2.0
SCOPE:
2.1
This procedure is applicable to all Autoclaves performance / re-qualifications
performed in Aurobindo Pharma Ltd. Unit-IV.
3.0
RESPONSIBILITY:
3.1
Validation
Group:
Is responsible for preparation of Autoclave
Qualification / Re-Qualification plan/ protocols and also responsible for
execution of qualification activity as per the approved protocol, with required
support from cross functional departments (User, Engineering, and QC).
3.2
Engineering
/ Instrumentation:
Engineering/Instrumentation department is responsible to review the
protocol, and support for the execution activity.
3.3
User
department:
Is
responsible to review the protocols, support the qualification activity
wherever applicable, and review the qualification data/ activity.
3.4
Quality
Control:
To
review the protocol and perform sample testing, wherever applicable.
3.5
Head- QA:
Head-QA is
responsible to approve the protocol and report.
4.0
ACCOUNTABILITY:
4.1
It is the responsibility of respective department
heads to ensure the compliance and the concerned personnel performing the
activities are trained on this SOP.
4.2
Head –
QA is accountable for overall compliance of the SOP.
5.0
DEFINITION:
5.1
Biological
indicator: An inoculated microbial carrier contained within its
primary pack ready for use.
5.2
Cold Spot:
The locations with in the load zone that achieves the lowest process
lethality (Fo) and / or the lowest distribution temperatures during
the sterilization process.
5.3
D-value: The exposure time under a defined set
of conditions to cause a 1-logarithm reduction in the population of a
particular microorganism.
5.4
Drain: Drain
which is situated at the lowest part of the sterilizer chamber to control the
discharge of air/non-condensable gases or air and condensate from the
sterilizer chamber.
5.5
Equilibration
time: The period that elapses between the attainment of the minimum exposure temperature
at the reference measure point (typically the drain) and the attainment of the
sterilization temperature at all points within the load. This period is an
indication of the ability to properly remove air and heat the load items;
consequently, it is typically only evaluated by placing HP probes in
porous/hard goods loads.
5.6
Lag Time: The time
difference between the attainment of the minimum sterilization temperature (any
point) and the attainment of the sterilization temperature at all points within
the load. It is typically only evaluated by placing HP probes in liquid loads (preferably
media).
5.7
Fo value: The time
(in minutes) required to provide the lethality equivalent to that which is
provided at 121°c for one minute.
5.8
Holding
/Hold time: Period for which the temperature of all points within
the sterilizer is held within the sterilization temperature band. (NOTE. The
holding time follows immediately after the equilibration time. The extent of
the holding time is related to the sterilization temperature).
5.9
Overkill: A cycle which
provides more than a 12-log reduction of a resistant biological indicator with
a known D-value of not less than 1 minute. This approach assures substantially
greater than a 12-log reduction of the bioburden and therefore only minimal
information on the bioburden is required.
5.10
Porous
Load: Material in an autoclave which is sterilized by heat transfer from
condensation of steam directly on to its contaminated (or potentially
contaminated) surfaces.
5.11
Probability
of a Non-Sterile Unit (PNSU): The number expressing the probability of
finding a non-sterile unit in a known number of sterilized units. For sterilization
processes in the healthcare industry a maximum probability of 1 non-sterile
unit in a million units is usual.
5.12
Sterility
Assurance Level (SAL): An estimate of the effectiveness of a
sterilization process generally developed through detailed knowledge of the
process itself and the organisms likely to be present.
5.13
Sterilization:
Process undertaken to render an object(s) sterile.
5.14
Sterilization
cycle : Automatic sequence of operating stages performed in a
sterilizer for the purpose of sterilization
5.15
Sterilization
temperature range: Range of temperatures, expressed as the sterilization
temperature and the maximum allowable temperature which may prevail throughout
the load during the holding time.
6.0
FLOW CHART :
6.1
Not
Applicable.
7.0
PROCEDURE:
7.1
Process
development:
7.1.1
Process
development studies will be performed to establish new parameters & new
load configuration and will be recorded in the format provided as an Annexure-1.
7.1.2
Qualification
Parameters shall be fixed based on the out come of the trail data and shall be
incorporated in to respective SOPs to be followed for further qualification
studies and / or routine usage.
7.1.3
Process/cycle development reports (Annexure-1) shall be archived along with
qualification documents in QA archival. These reports shall be the basis to
prepare user SOPs and qualification protocols etc.
7.2
Protocol Preparation
And Approval:
7.2.1
Autoclave qualification Plans / protocols shall
be prepared as per the SOP QA076 (Performance qualification /
Re-qualification).
7.2.2
Protocol should contain the details about all
the tests and acceptance criteria for that particular qualification /
re-qualification.
7.2.3
Performance Qualification / Re-qualification
execution shall be carried out by responsible cross functional teams of user,
engineering and QA.
7.2.4
Inclusion of any new load shall be qualified,
through respective protocol or with an addendum in case of independent
activity. This load shall be a part of plan & protocol for subsequent
routine requalification based on the process developments, as applicable.
7.2.5
All the applicable tests described in this SOP
shall be included in the protocol.
7.3
Prerequisites
to start execution:
7.3.1
Note down all the prerequisites checks and other
checks to be performed as described in the respective templates but not limited
to, along with the defined and measurable specific acceptance criteria.
7.3.2
Calibration status of the all temperature and
pressure devices of the respective steam sterilizer/Autoclaves should be
reviewed and recorded before commencement of performance
qualification/re-qualification.
7.3.3
Ensure that Data logger and temperature sensors
used in the qualification activity, shall be calibrated and with in the due
period, prior to start of activity.
7.3.4
All
other operational attributes & SOPs identified in the protocol shall be in
place prior to start of the activity.
7.4 Verification of Vacuum Leak Test:
7.3.5
Check and ensure that the vacuum leak test
parameters are as mentioned in the respective operation SOP before start the
cycle.
7.3.6
The prime objective of this test is to validate
the integrity of the autoclave chamber.
7.3.7
If vacuum leak test fails, rectify leakage and
perform vacuum leak test again until it passes.
7.3.8
The
maximum acceptable leak should be less than 1.3 mbar/minute or 0.013 bar over a period of 10 minutes or as per design
specifications.
7.5 Verification of Bowie-Dick Test:
7.3.9
The Bowie-Dick Test (air removal test) is to
evaluate the efficiency of air removal during the pre-vacuum phases of
sterilization cycle. The Bowie-Dick test is a diagnostic test of a sterilizer's
ability to remove air from the chamber and prevents residual air remaining in
porous masses.
7.3.10 A
ready “Bowie and Dick test kit” or “
7.3.11 Check
and ensure the validity of the test kit / sheet to be use with respect to its
expiry date.
7.3.12 Place
the “Bowie-Dick test kit” near to drain at a distance of above 5 cm.
7.3.13 Select
the
7.3.14 The
Bowie-Dick cycle shall be run for a hold period of 3.5 minutes at 134-138°C
unless other conditions for e.g. 17 minutes at 121°C or specifically recommended
by suppliers of proprietary kits.
7.3.15 After
completion of the cycle, retrieve and examine the test sheet for the compliance
against the acceptance criteria (Uniform color change should observe on
Bowie-dick indicator).
7.3.16 Document
the test details and attach the test sheet to the protocol.
7.6 Empty Chamber Heat Distribution Studies:
7.3.17 Empty
Chamber Heat Distribution studies shall be done for new autoclaves or for
autoclaves moved from one location to another or if steam supplies are
significantly changed studies and no need to be perform during the periodic
re-qualification of the steam sterilizers/Autoclaves.
7.3.18 Each
Empty Chamber Heat Distribution trial shall be done using at least 12 sensors
or shall be decided based on the size / volume of the equipment
7.3.19 One
shall be located in the drain
7.3.20 One
shall be located adjacent to the control or monitoring sensor within the
chamber
7.3.21 One
shall be located at the geometric dead centre of the chamber
7.3.22 The
remain shall be distributed throughout the chamber
7.3.23
7.3.24 Place
the data logger, pre calibrated temperature sensors (identified with numbers)
inside sterilizer chamber, as per the temperature sensor location diagram
enclosed for the respective protocol by covering all locations of the
sterilization chamber.
7.3.25 Select
the sterilization cycle and verify the sterilization cycle parameters with
respective standard operating procedure of the sterilizer/Autoclave.
7.3.26 Carry
out the empty chamber heat distribution studies with temperature logging
interval of not more than 5 seconds.
7.3.27 After
completion of sterilization cycle stop the data logger and open the non sterile
door of the sterilizer/Autoclave.
7.3.28 Take
and check out the Temperature profile from the Data logger, equipment temperature
printout and strip chart recorder of machine and attach with the executed
protocol.
7.3.29 Calculate
the maximum, minimum, average temperatures within the probes during
sterilization hold period of Empty Chamber Heat Distribution cycle.
7.3.30 Photographs
showing placement of sensors should be included in documentation.
7.3.31 Three
consecutive successful runs of empty chamber heat distribution shall be
performed during initial performance qualification to confirm uniform heat
distribution in the sterilizer chamber by mapping the temperatures at
different locations and to identify the cold spot (if any) at which the lowest
Fo- value has accumulated with in the chamber throughout end of the hold
period.
7.3.32 If
more than one sensor fails (except sensor located at drain point) during the
study, shall be considered invalid and may be repeated.
7.3.33 Empty
chamber runs are not generally done with a completely empty chamber. It is
permitted to have a “rack” within the chamber to support the sensors.
7.3.34
7.3.35 Check
the calibration reports for its compliance with respect to the acceptance
criteria and attach the Calibration reports along with executed protocol.
7.3.36 The
F0 - value of all the temperature sensors of data logger should not be less
than of sterilization hold time.
7.3.37 The
temperature measured, throughout the sterilization holding time, should be
within the 121.0 to 124.0 °C.
7.3.38 Throughout
the dwell time, the temperature variation of each sensor does not fluctuate by
more than 20C.
7.3.39 Throughout
the dwell time at that particular time the temperature variation of all sensors
does not fluctuate by more than 20C.
7.4 Loaded Chamber Heat Distribution Studies:
7.3.40 Loaded
Chamber Heat Distribution studies shall be done for new Autoclaves or for
autoclaves moved from one location to another or if steam supplies are
significantly changed, if any change in the load pattern, any addition of new
loads. And no need to perform during the periodic re-qualification of the Autoclaves.
7.3.41 Each
Loaded Chamber Heat Distribution trial shall be done using at least 12 sensors
or shall be decided based on the size / volume of the equipment
7.3.42 One
shall be located in the drain
7.3.43 One
shall be located adjacent to the control or monitoring sensor within the
chamber
7.3.44 One
shall be located at the geometric dead centre of the load
7.3.45 The
remain shall be distributed throughout the load
7.3.46 Sensors
shall be placed beside (not within) load items
7.3.47
7.3.48 Place
the data logger temperature sensors (identified with numbers) inside the
sterilizer chamber beside (not within) the load, as per the temperature sensor
location diagram enclosed in authorized protocol covering of all critical
locations in the sterilization chamber.
7.3.49 Select
the sterilization cycle and verify the sterilization cycle parameters with
respective standard operating procedure of the sterilizer/Autoclave.
7.3.50 Carry
out the loaded chamber heat distribution studies with temperature logging
interval of not more than 5 seconds.
7.3.51 After
completion of sterilization cycle stop the data logger and open the non sterile
door of the sterilizer/Autoclave.
7.3.52 Take
and check out the Temperature profile from the Data logger, equipment
temperature printout and strip chart recorder of machine and attach with the executed
protocol.
7.3.53 Calculate
the maximum, minimum, average temperatures within the probes during
sterilization hold period of Loaded Chamber Heat Distribution cycle
7.3.54 Photographs
showing the loads and placement of sensors should be included in
documentation.
7.3.55 Three
consecutive successful runs of loaded chamber heat distribution with maximum
load in its defined configuration shall be performed during initial performance
qualification to confirm uniform heat distribution in the sterilizer chamber by
mapping the temperatures at different locations and to identify the cold
spot (if any) at which the lowest Fo- value has accumulated to the end of the
hold period.
7.3.56 The
“cold spot” location obtained from Loaded Chamber Heat Distribution Trials shall
be compared to the findings obtained from Empty Chamber Heat Distribution
Trials.
7.3.57 If
more than one sensor fails (except sensor located at drain point) during the
study, shall be considered invalid and may be repeated.
7.3.58 Check
the calibration reports for its compliance with respect to the acceptance
criteria and attach the Calibration reports along with executed protocol.
7.3.59 The
Fo - value of all the temperature sensors of data logger should not be less
than of sterilization hold time.
7.3.60 The
temperature measured, throughout the sterilization holding time, should be
within the 121.0 to 124.0 °C.
7.3.61 Throughout
the dwell time, the temperature variation of each sensor does not fluctuate by
more than 20C.
7.3.62 Throughout
the dwell time at that particular time the temperature variation of all sensors
does not fluctuate by more than 20C.
7.1Loaded Chamber Heat Penetration with Biological
indicator Studies:
7.3.63 These
studies shall be done for new autoclaves or for Autoclaves moved from one
location to another or if steam supplies are significantly changed or for the
introduction of new items or new load configurations.
7.3.64 These
studies shall be carried out for all types of load configurations and load
patterns individually.
7.3.65 Each
trial shall be done using at least 12 sensors or shall be decided based on the
size / volume of the equipment.
7.3.66 One
shall be located in the drain
7.3.67 One
shall be located adjacent to the control or monitoring sensor within the
chamber
7.3.68 The
remain shall be placed within items making up the load and shall be distributed
throughout the load.
7.3.69 If
a “cold spot” has been identified in previous trials of the autoclave, sensors
shall be located at or close to any “cold spot” which may have been identified.
7.3.70
7.3.71 Place
the data logger temperature sensors (identified with numbers) inside the load,
as per the temperature sensor location diagram enclosed for the respective
protocol.
7.3.72 Each
sensor shall be placed within items at locations from which air may be most
difficult to remove and to which steam may be most difficult to penetrate.
7.3.73 Place
pre enumerated biological indicators (20 numbers) of Geobacillus
stearothermophilus (carrier shall be paper strips having minimum106
spores per strip with D121-values of between 1.5 and 4.0 minutes) with properly
marked details in the middle of the sterilization load near each temperature
sensor kept to check heat penetration, and also at the locations where sensor
can not be placed but the location is defined as difficult for steam
penetration (if any).
7.3.74 Note:
Biological indicators shall be placed only in the third run of each loaded heat
penetration study.
7.3.75 In
case of rubber stoppers load instead of biological indicator spore strips,
spiked rubber stoppers (20 numbers) shall be used. Spiked rubber stopper shall
be kept in tyvek or parchment paper to expose in autoclave.
7.3.76 In
case of fluid containers load (e.g. media loads in QC sterilizers/Autoclave)
instead of biological indicators spore strip, liquid ampoule biological
indicators (20 numbers) shall be used.
7.3.77 There
shall be a documented justification for the items selected and for the
locations within the items selected for BI placement.
7.3.78 Select
the sterilization cycle and verify the sterilization cycle parameters with
respective standard operating procedure of the sterilizer/Autoclave.
7.3.79 Carry
out these studies with temperature logging interval of not more than 5 seconds.
7.3.80 After
completion of sterilization cycle stop the data logger, open the non sterile
door of the sterilizer/Autoclave and take out the Biological indicators from
the load & send to Microbiological Lab for testing as per the respective
SOP.
7.3.81 Take
and check out the Temperature profile from the Data logger, equipment
temperature printout and strip chart recorder of machine and attach with the executed
protocol.
7.3.82 Check
the equilibration time.
7.3.83 Calculate
the maximum, minimum, average temperatures within the probes during
sterilization hold period of Loaded Chamber Heat Penetration cycle.
7.3.84 Photographs
showing the loads and placement of sensors should be included in documentation.
7.3.85 If
more than one sensor fails (except sensor located at drain point) during the
study, shall be considered invalid and may be repeated.
7.3.86 Temperature
sensors used should be calibrated after completion of activity (post
calibration) to ensure that the temperature measurement system is accurate and
precise.
7.3.87 Check
the calibration reports for its compliance with respect to the acceptance criteria
and attach the Calibration reports along with executed protocol.
7.3.88 At
least three (3) successive Heat Penetration trials shall be performed complying
with the acceptance criteria for initial qualification by placing the
biological indicators in the third run of each defined load configuration.
7.3.89 Consider
the lag time for liquid loads and record it.
7.3.90 The
F0- value of all the temperature sensor of data logger should be equal to or
more than sterilization hold time set (except liquid or nutrient media loads).
7.3.91 For
Nutrient media load, F0 - value of all the temperature sensor of data logger
should be not less than 15 minutes.
7.3.92 The
temperature measured, throughout the sterilization holding time, should be
within 121.0 to 124.0 °C.
7.3.93 The
equilibrium time should not be more than 30 seconds.
7.3.94 The
equilibrium time is not applicable for liquid/ nutrient media loads.
7.3.95 Throughout
the dwell time, the temperature variation of each sensor does not fluctuate by
more than 20C.
7.3.96 Throughout
the dwell time at that particular time the temperature variation of all sensors
does not fluctuate by more than 20C.
7.4 Loaded Chamber Heat penetration Studies with biological indicators
(Shortened holding period):
7.3.97 Test
procedure shall be followed as mentioned in the section 7.8.
7.3.98 Sterilization
hold time for all the loads in this study shall be less than sterilization hold
time set in the loaded heat penetration studies. This study shall be performed
as a one time activity with one run only.
7.3.99 The
F0- value of all the temperature sensor of data logger should be equal to or
more than sterilization hold time set. (except liquid or nutrient media load)
7.3.100 For
Nutrient media load, F0 - value of all the temperature sensor of data logger
should be not less than 15 minutes.
7.3.101 The
temperature measured, throughout the sterilization holding time, should be
within 121.0 to 124.0 °C.
7.3.102 The
equilibrium time should not be more than 30 seconds.
7.3.103 The
equilibrium time is not applicable for liquid/ nutrient media loads.
7.3.104 Throughout
the dwell time, the temperature variation of each sensor does not fluctuate by
more than 20C.
7.3.105 Throughout
the dwell time at that particular time the temperature variation of all sensors
does not fluctuate by more than 20C.
7.3.106 Estimation
of Fo Value:
7.3.107 To
identify number of equivalent minutes of sterilization at temperature 121.1°C
delivered to an item or unit of product calculated using a Z-value of 10°C
temperature.
7.3.108 Calculate
the Fo value at each temperature mapping probe for each time interval during
dwell period by using the following formula:
7.3.109 F0: ∑ 10 (T-121.1)/z Δ t
7.3.110 F0 value is time that is equivalent to the
sterilization effect at 121.1 ºC.
7.3.111 T = Product temperature at specific time in ºC
7.3.112 Δ t = Time interval between temperature
measurement (in minutes).
7.3.113 Z =
Temperature required to change the D value by a factor of 10.
7.3.114 D value
is time required to reduce a microbial population by a one-logarithm reduction
7.3.115 Note: If the Δt is 5 seconds and Z value is 10ºC
for sterilization study so the final formula for calculation of Fo values is:
7.3.116 F0 = ∑10 (T-121.1)/10×0.08
7.3.117 Calculate
cumulative Fo value by summing the Fo values for every 5 seconds obtained
during sterilization hold period by using the following formula:
7.3.118 F0 = ∑ (sum of lethal rates)
7.4
Re-qualification
Programmes:
7.4.1
Re-qualification shall be performed once in six
months at minimum.
7.4.2
Heat Penetration and Biological Qualification studies
shall be done as part of a time-related re-qualification programme for every
autoclave.
7.4.3
One Heat Penetration and Biological
Qualification trial shall be done on every defined load (including minimum
loads) on each autoclave at least once in 2 years at minimum.
7.4.4
Any modifications in the existing load,
incorporation of new loads shall adequately qualify through RQ / Addendum. The
number of cycles shall be determined based on the impact assessment performed
for respective change control.
7.4.5
A comparison shall be made between
requalification data and initial qualification, with suitable comments in
summary / conclusion. Any significant variation shall be documented with
adequate rationale and proposed actions to prevent potential failures.
7.5
Failure:
7.5.1
Failure to comply with acceptance criteria in
any initial qualification study which after investigation results in changes
7.5.2
The engineering or software controls of the
autoclave or of the steam supply shall require all qualifications from Empty
Chamber Heat Distribution onwards to be repeated.
Ø To defined load configurations or orientation of items
within loads shall require all qualifications from Loaded Chamber Heat
Distribution onwards to be repeated.
7.5.3
Failure to comply with acceptance criteria in
re-qualification Heat Penetration or Biological Qualification study shall be
handled through the SOP CQA-CP-GEN-014.
7.6
Documentation:
7.6.1
The out come of qualification study with respect
to change in load configuration, process parameters etc., shall be incorporated
adequately in respective SOPs by user, where ever applicable. Validation group
/ QA shall ensure this requirement prior to close the executed report.
7.6.2
At the end of each temperature mapping study,
data recorded in the data logger temperature mapping storage devise, shall be
printed and enclosed as an annexure for executed protocol with sign and date.
Required data (For e.g. F0 (in minutes), minimum, maximum and average
temperatures) shall be collected from the original print out and recorded in
the protocol.
7.6.3
If required data is not available from data
loggers print out, original temperature mapping data shall be converted in to
MS-EXCEL sheet and F0 (in minutes), minimum, maximum and average temperatures
shall be calculated.
7.6.4
Equipment temperature printout and strip chart
recorder of machine shall be attached to executed protocol.
7.6.5
Specified Load details, Probe location diagrams
& justification and photographs (Empty chamber and loaded chamber) shall be
attached as an annexure for executed protocol.
7.6.6
Data logger, temperature sensors (Pre &
Post) calibration details / certificates shall be attached to the executed
protocol.
7.6.7
Process/Cycle development studies shall be
recorded in Annexure-1.
8.0
ABBREVIATION:
|
S. No. |
Abbreviation |
Full
Description |
|
2. |
BI’s |
Biological
Indicators |
|
3. |
GPT |
Growth
Promotion Test |
|
4. |
HD |
Heat
Distribution |
|
5. |
HP |
Heat
Penetration |
|
6. |
NA |
Not
Applicable |
|
7. |
NMT |
Not More
Than |
|
8 |
PLC |
Programme
Logic Controller |
|
9. |
PNSU |
Probability of a Non-Sterile Unit |
|
10. |
PQ |
Performance
Qualification |
|
11. |
RQ |
Re-Qualification |
|
12. |
SAL |
Sterility Assurance Level |
|
13. |
SOP |
Standard Operating
Procedure |
|
14. |
SP |
Sterile
process |
|
15. |
QA |
Quality
Assurance |
|
16. |
QC |
Quality
Control |
|
17. |
VMP |
Validation
Master Plan |
9.0
SAFETY, HEALTH AND ENVIRONMENT:
·
Identify all the
potential hazards during the qualification activity and list adequate measures
to be taken, to eliminate the hazards, while developing the qualification
protocol
10.0
REFERENCE:
|
S. No. |
Topic
of the SOP |
SOP
No. (Current Version) |
|
1. |
Validation Master Plan |
DOC NO.: APL-VMP-02. |
|
2. |
Performance
qualification / Requalification |
SOP QA076-00 |
|
3. |
Sterilisation of porous loads by moist Heat in
Autoclaves |
APL-Quality Policy–SP-006 (Version:1.0.0.0) |
|
4. |
Numbering and Control of Validation/ Qualification
protocols |
SOP QA015-06 |
|
5. |
Good Documentation Practices |
SOP QA010-04 |
|
6. |
Reporting and monitoring of process non conformance in the
automated quality management system software |
SOP CQA-CP-GEN-014 (Version:2.0.0.0) |
·
SHTM 2010
·
EN285 (sterilization by autoclaves).
·
PDA Tech. Report-1. “Steam sterilization”
11.0
ANNEXURE:
·
Annexure-1 - Process/Cycle
Development Report.
|
CHANGE
HISTORY |
||
|
Version |
Supersedes |
Changes
made |
|
00 01 |
NA QA081-00 |
1. First
issue 1. Lag time definition
included in the SOP. 2. Process
development procedure, format to record the results (Annexure-1) included in
the SOP. 3. Side heading
verification of calibration status of temperature sensors and data logger
changed as prerequisites to start execution. 4. Expanded
Requalification programme. 5. Procedure amended
vide change request APL-FU4-CC-12-0073. |
ConversionConversion EmoticonEmoticon